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3. CP - Diseases of the Respiratory System > (19) Mycobacterial diseases > Flashcards

(19) Mycobacterial diseases Flashcards

1
Q

Why type of bacteria is mycobacteria?

A

Slender bacillus

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2
Q

How are mycobacteria different to all other bacterial genera?

A
  • usually waxy cell wall - high lipid content

- slow growing - different media requirements

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3
Q

What are the different staining characteristics of mycobacteria?

A
  • poor take up of standard Gram’s stains
  • gram positive: Ghost cells
  • “acid fast bacilli” AFBs
  • Ziehl Neelsen (ZN) staining used
  • Phenol auramine
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4
Q

Which mycobacteria cause tuberculosis?

A

M. tuberculosis complex:

  • M. tuberculosis
  • M. bovis
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5
Q

Which mycobacterial cause leprosy?

A

M. leprae

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6
Q

Which mycobacterial cause fish tank granuloma/mycobacterium marinum?

A

“Atypical mycobacteria”

  • M. avium complex
  • M. kansasii
  • M. marinum
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7
Q

How much of the world population is infected with M. tuberculosis?

A

One third of the world population

“global emergency”

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8
Q

How many deaths a year are there of tuberculosis?

A

2 millions deaths per year

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9
Q

What is the commonest infectious cause of adult deaths?

A

M. tuberculosis

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10
Q

In Sub-Saharan Africa, you often get co-infection of M. tuberculosis with what?

A

HIV

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11
Q

What is happening in the “developed world”?

A
  • increased global migration from endemic areas
  • increased travel
  • breakdown of control programmes
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12
Q

How many in patients for tuberculosis were born abroad?

A

Over 70%

Black African, Pakistani, Indian

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13
Q

The majority of UK tuberculosis cases are of what age?

A

Majority (60%) are young adults (15-44)

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14
Q

When was there a recent peak in UK tuberculosis cases?

A

2011

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15
Q

There is geographical variation in UK tuberculosis incidence. Where has highest rates?

A

London

lowest in the South West

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16
Q

What is the pathogenesis of tuberculosis?

A
  • inhalation of infected respiratory droplets

- usually pulmonary disease (>50% of cases)

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17
Q

Describe the stages of primary tuberculosis?

A
  1. primary acquisition/infection and body’s reaction
  2. periphery of lung midzone is most common site
  3. inhaled bacilli phagocytosed by macrophages
  4. hilar lymph nodes “Ghon focus”
  5. intracellular multiplication
  6. dissemination via lymphatic system/bloodstream
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18
Q

What is the most common site of primary tuberculosis infection?

A

Periphery of lung midzone

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19
Q

What is Gohn focus?

A

Primary lesion caused by mycobacterium bacilli (tuberculosis) developed in the lung of a nonimmune host

Small area of granulomatous inflammation, only detectable by [chest X-ray] if it calcifies or grows substantially

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20
Q

The body responds to M. tuberculosis infection by tubercle formation. Describe this process

A
  • granuloma
  • cell-mediated immune response
  • central area of epithelioid cells, giant cells
  • surrounding lymphocytic cell infiltration
  • central area caseous necroses
  • fibrosis/calcification of lesions
  • bacilli slowly die /may remain viable for 20 years
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21
Q

What kind of necrosis occurs in the centre of the tubercle/granuloma?

A

Caseous necrosis

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22
Q

The macrophages in granulomas (in the central area of the tubercle) are often referred to as what?

A

Epithelioid cells

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23
Q

What are the mild clinical symptoms you may get in primary tuberculosis infection? (symptoms may be absent)

A

“Influenza-like” syndrome

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24
Q

How would you diagnose a primary tuberculosis infection?

A
  • chest X-ray

- tuberculin skin test conversion

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25
Q

What causes reactivation tuberculosis?

A
  • lowered immunity
  • malnutrition
  • alcoholism
  • debilitating illness
  • in Western countries: men over 50 years old
  • HIV infection
  • silicosis, chronic renal failure, gastrectomy..
  • anti TNFa blockage eg. infliximab
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26
Q

What happens to the tubercles in reactivation tuberculosis?

A
  • coalescing tubercles
  • central caseous necrosis
  • cavitation (extensive necrosis, high organism load, risk of transmission)
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27
Q

Where in the lungs does tuberculosis infection tend to occur?

A

Lung apices

due to highest oxygen tension

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28
Q

Reactivation tuberculosis is symptomatic. What are the symptoms

A
  • chronic productive cough
  • haemoptysis
  • weight loss
  • fever
  • night sweats
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29
Q

What is miliary tuberculosis?

A

Widespread dissemination of Mycobacterium tuberculosis via haematogenous spread

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30
Q

Who does dissemination of tuberculosis occur in?

A
  • very young/old

- immunocompromised

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31
Q

What happens on reactivation of tuberculosis that causes dissemination?

A

Erosion of necrotic tubercle into blood vessel

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32
Q

What are the extra-pulmonary sites of tuberculosis infection? (on dissemination)

A
  • widespread infection, including meningitis
  • pleura
  • lymph nodes
  • kidney
  • epididymis
  • bone
  • intestines
  • brain/meninges
  • pericardium
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33
Q

in 2013, 52.1% of TB cases were pulmonary. Where were 23.9% of cases?

A

Extra-thoracic lymph nodes

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34
Q

What percentage of TB cases in the UK are TB meningitis?

A

2%

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35
Q

What are the symptoms of TB meningitis?

A
  • often insidious onset
  • unidentified fever
  • personality change
  • focal neurological deficit (basilar inflammation)
  • mild headache/meningism
  • map lack constitutional quartet (fever, night sweat, anorexia, weight loss)
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36
Q

What is the constitutional quartet of TB symptoms?

A
  • fever
  • night sweats
  • anorexia
  • weight loss
37
Q

What is involved in TB diagnosis? (non-microbiological)

A
  • index of suspicion
  • clinical
  • radiology (CXR)
  • histology
  • skin testing
  • blood test: interferon-y release assay: IGRA
38
Q

What is the purpose of microbiological diagnosis of TB?

A
  • confirmation of diagnosis
  • drug sensitivities
  • molecular typing profile “MIRUs”
  • “fresh” samples/tissue ie. NOT formalin fixed
39
Q

What makes up microbiological diagnosis of TB?

A
  • sputum testing-
  • direct microscopy for AFBs (acid fast bacilli)
  • culture
40
Q

What is needed to do a TB microbiology diagnosis from sputum?

A

3 “early morning” specimens

3 taken > 8 hours apart with > 1 early morning

41
Q

How is direct microscopy for AFBs useful in TB diagnosis?

A

Over 5000 organisms per ml of sputum = “smear positive”

42
Q

How are samples from suspected TB cultured?

A
  • Lowenstein-Jensen solid media: 3-4 weeks

- Broth culture: automated, usually

43
Q

What is then done to a positive AFB culture?

A
  • referred to regional reference laboratory
  • species identification
  • sensitivities (within 2 weeks)
  • strain typing
44
Q

What would you do to get a sample in the case of lack of sputa?

A
  • induced sputa (nebulised saline)
  • bronchial aspirates (environmental mycobacteria)
  • gastric aspirates
45
Q

What renal contents would you use in microbiology?

A
  • “sterile” pyuria (pus in the urine)

- early morning urine x3

46
Q

How is CSF useful in microbiological diagnosis?

A
  • cell count, protein, glucose
  • microscopy/culture
  • “adequate” volume >6mls - increased yield
47
Q

What are the benefits/diadvantages of using nucleic acid amplification (polymerase chain reaction PCR)?

A
  • rapid
  • less sensitive than culture
  • expensive
  • not 100% specific (false positives)
48
Q

What is the Xpert MTB/RIB test?

A

Nucleic acid amplification test, automated diagnostic test that can identify Mycobacterium tuberculosis (MTB) DNA and resistance to rifampicin (RIF)by nucleic acid amplification test

49
Q

What are the benefits of Xpert MTB/RIF test?

A
  • direct to sputum
  • results in 2 hours
  • clinic based
  • 99% specificity
50
Q

What is DOTS?

A

Directly observed treatment, short-course

Tuberculosis control strategy recommended WHO

Prevents resistance development

51
Q

What is the standard treatment for pulmonary TB?

A

2 months - isoniazid, rifampicin, pyrazinamide, ethambutol/streptomycin
4 months - isoniazid, rifampicin

52
Q

How long is treatment for TB in sites other than the lungs (except meningeal)?

A

Standard 6 month regimen

53
Q

How long is the treatment for meningeal TB?

A

12 months of therapy

54
Q

How would you treat meningitis and pericarditis caused by TB?

A

Initial treatment also with corticosteroids

55
Q

What are the second line agents that you would use for TB when you have drug resistance?

A
  • amikacin
  • ethionamide/prothionamide
  • cycloserine
  • fluoroquinolones: ciprofloxacin, moxifloxacin
56
Q

What does MDR stand for?

A

Multi-drug resistant

57
Q

What is MDR TB resistant to?

A
  • isoniazid

- rifampicin

58
Q

What does XDR stand for?

A

Extensive drug resistant

59
Q

What is XDR TB resistant to?

A
  • isoniazid
  • rifampicin
  • fluoroquinolone
  • injectable amikacin or capreomycin
60
Q

Give 3 examples of new drugs for TB?

A
  • bedaloquine
  • delamanid
  • Pa-824
61
Q

What are the benefits of shorter regimens for standard Rx?

A
  • improve completion rates
62
Q

Is TB a notifiable disease?

A

Yes

63
Q

How do you screen for TB/previous exposure to TB?

A

Tuberculin skin test/Mantoux test - inject a solution containing a protein derived from tuberculosis bacteria just under the top layer of skin on the forearm - skin will react to the antigens by developing a firm red bump at the site within 2 days if you have been exposed

64
Q

What blood test would you do for TB?

A

Interferon-y release assay -rely on the fact that T cells will release IFN-γ when exposed to TB antigens

65
Q

Other than tuberculin skin test and IFN-y release assay, what else can you do to detect TB?

A

Chest X-ray

66
Q

Describe the Mantoux test (TST)?

A
  • inject purified protein derivative (MTB extract)
  • cell-mediated immune response
  • read at 48-72 hours
67
Q

Give 2 TB specific antigens

A

ESAT6

CFP10

(don’t cross react with M bovis BCG)

68
Q

What do BCG stand for?

A

Bacille Calmette Guerin

69
Q

What does the BCG vaccine contain?

A

Attenuated stain M bovis

70
Q

BCG vaccine has limited efficacy. Who is it given to?

A
  • under 35 considered at risk
  • no evidence of effect over 35
  • risk of exposure (occupational)
71
Q

Other than the BCG vaccine, how else can we prevent TB?

A

Chemoprophylaxis

3 months IRF/INH or 6 months INH

72
Q

What is RIF and INH?

A

RIF = rifampicin/rifampin

INH = isoniazid

73
Q

What is nontuberculous mycobacteria? (NTM)

A
  • also known as environmental mycobacteria, or atypical mycobacteria
  • mycobacteria which do not cause tuberculosis or leprosy
  • NTM are widely distributed in the environment, particularly in wet soil
  • colonisation
  • lack of person to person transmission
74
Q

What is mycobacterium avium complex?

A
  • MAC

- microbial complex of Mycobacterium avium and Mycobacterium intracellulare

75
Q

Who is most affected by mycobacterium avium complex (MAC)?

A

Those with HIV and low CD4 cell count

  • causes disseminated disease in up to 40% of patients with HIV
76
Q

How does mycobacterium avium complex affected those not infected with HIV?

A
  • tuberculosis-like pulmonary infection

- cervical lymphadenitis in young children

77
Q

What is the treatment for mycobacterium avium complex?

A
  • combined
  • prolonged
  • macrolide (clarithromycin or azithromycin)
78
Q

What is leprosy also called?

A

Hansen’s disease

79
Q

What causes leprosy?

A

M. leprae

80
Q

Which animal is often affected with M. leprae?

A

Nine banded armadillo

81
Q

Is M. leprae culturable?

A

Non culturable in vitro

82
Q

What are the 2 extreme clinical forms of immune response to leprosy?

A
  • tuberculoid

- lepromatous

83
Q

Describe the tuberculoid immune response to leprosy

A
  • macules/plaques

- nerve: ulnar, peroneal

84
Q

Describe the lepromatous immune response to leprosy

A
  • subcutaneous tissue accumulation

- ear lobes, face - leonine facies

85
Q

What is leonine facies?

A

A face that resembles that of a lion.

It is seen in multiple conditions and has been classically described for Lepromatous leprosy

86
Q

What is the treatment for leprosy?

A
  • dapsone
  • rifampicin
  • clofazimine
87
Q

Give an example of a case of leprosy

A
  • Bangladeshi lady
  • came to UK 5 years ago
  • rash on face since birth of son
  • initially only on face and neck
  • then on arms, legs, abdomen, chest and back
  • patches itchy and sore
  • non-responsive to steroids, antihistamines, emollients
  • lesions began as hypo pigmented skin
  • slightly reduced sensation on areas affected
  • biopsy shows sheets of histiocytes in vague granulomatous pattern
  • probable perineural invasion
  • ziehl-neelsen and wade-fife staining shows histiocytes “teaming with mycobacteria”
  • biopsy positive on PCR for M leprae DNA
88
Q

When might you suspect TB clinically?

A
  • fever
  • weight loss
  • night sweats
  • chronic cough
  • CXR changes
  • request AFBs

3. CP - Diseases of the Respiratory System (4 decks)

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